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Widespread aneuploidy revealed by DNA microarray expression profiling

Abstract

Expression profiling using DNA microarrays holds great promise for a variety of research applications, including the systematic characterization of genes discovered by sequencing projects1,2. To demonstrate the general usefulness of this approach, we recently obtained expression profiles for nearly 300 Saccharomyces cerevisiae deletion mutants3. Approximately 8% of the mutants profiled exhibited chromosome-wide expression biases, leading to spurious correlations among profiles. Competitive hybridization of genomic DNA from the mutant strains and their isogenic parental wild-type strains showed they were aneuploid for whole chromosomes or chromosomal segments. Expression profile data published by several other laboratories also suggest the use of aneuploid strains. In five separate cases, the extra chromosome harboured a close homologue of the deleted gene; in two cases, a clear growth advantage for cells acquiring the extra chromosome was demonstrated. Our results have implications for interpreting whole-genome expression data, particularly from cells known to suffer genomic instability, such as malignant or immortalized cells.

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Figure 1: Detection of a chromosome VII expression bias in erg4Δ and ecm18Δ/ecm18Δ mutants by expression profiling, and confirmation of aneuploidy by two-colour hybridization of genomic DNA to DNA microarrays.
Figure 2: Expression profiling data in the literature consistent with aneuploidy.
Figure 3: Selection for aneuploidy in rnr1Δ and rps24aΔ /rps24aΔ mutants.
Figure 4: Segmental aneuploidy in an rpl20aΔ/rpl20aΔ mutant.
Figure 5: Spurious correlation between two mutants displaying a large transcriptional signature resulting from aneuploidy.

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Acknowledgements

We thank C. Boone, A. Murray, F. Spencer, N. Hastie, L. Hartwell, R. Stoughton and D. Shoemaker for their comments on the manuscript; P. Paddison for discussions on the implications of aneuploidy in human cancer; and our colleagues in the academic community for making full data sets publicly available. This work was supported by Rosetta Inpharmatics, Inc.

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Correspondence to Matthew J. Marton.

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Hughes, T., Roberts, C., Dai, H. et al. Widespread aneuploidy revealed by DNA microarray expression profiling . Nat Genet 25, 333–337 (2000). https://doi.org/10.1038/77116

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